Abstract
BackgroundExtracellular vesicles are membrane vesicles that are released into the extracellular environment and accumulate in the circulation in vascular disease. We aimed to quantify circulating extracellular vesicles in pregnant women with type 1 diabetes and to examine associations between extracellular vesicle levels, continuous glucose measures, and pregnancy outcomes.MethodsWe used plasma samples from the Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial study and quantified circulating extracellular vesicles by flow cytometry (n = 163). Relationships with clinical variables were assessed by repeated measures correlation. Logistic regression was used to assess associations between elevated extracellular vesicle levels and pregnancy outcomes.ResultsPlatelet extracellular vesicle levels were inversely associated with glucose time above range and glycaemic variability measures (P < 0.05). A weak positive association was observed between endothelial extracellular vesicles and mean amplitude of glycemic excursion (P < 0.05). In a univariate logistic regression model, high baseline endothelial extracellular vesicles was associated with increased risk of neonatal intensive care unit (NICU) admission (OR: 2.06, 1.03–4.10), and respiratory distress requiring ventilation (OR: 4.98, 1.04–23.92). After adjusting for HbA1c and blood pressure the relationship for NICU admission persisted and an association with hyperbilirubinemia was seen (OR: 2.56, 1.10–5.94). Elevated platelet extracellular vesicles were associated with an increased risk of NICU admission (OR: 2.18, 1.04–4.57), and hyperbilirubinemia (OR: 2.61, 1.11–6.12) after adjusting for HbA1c and blood pressure.ConclusionsHigh levels of extracellular vesicles in early pregnancy were associated with adverse neonatal outcomes. Assessment of extracellular vesicles may represent a novel approach to personalized care in type 1 diabetes pregnancy.
Highlights
Extracellular vesicles are membrane vesicles that are released into the extracellular environment and accumulate in the circulation in vascular disease
extracellular vesicles (EVs) levels throughout pregnancy We first examined levels of circulating platelet, endothelial, leukocyte, and total EVs to determine if levels change throughout type 1 diabetes pregnancy
A weak positive correlation between endothelial EVs and mean amplitude of glycemia excursion (MAGE) was observed but this was not accompanied by associations with other glycemic variability markers including Coefficient of variation (CV) and Standard deviation (SD)
Summary
Extracellular vesicles are membrane vesicles that are released into the extracellular environment and accumulate in the circulation in vascular disease. We aimed to quantify circulating extracellular vesicles in pregnant women with type 1 diabetes and to examine associations between extracellular vesicle levels, continuous glucose measures, and pregnancy outcomes. Maternal vascular health is a critical determinant of pregnancy outcomes and endothelial injury/dysfunction may play a causal role in acute and longer-term maternal fetal health outcomes [1, 2]. Impairment in endothelial function (assessed by flow-mediated dilatation) is observed in women with preeclampsia as compared to women without complications which highlights the important role of the endothelium in disease pathogenesis [5, 6]. The use of real time continuous glucose monitoring has been shown to improve maternal and neonatal outcomes, its effect on maternal vascular health is not known
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